Abstract
In this paper, we propose a novel cell self-loading and patterning device for quantitatively study density effect on cell behaviors. Using this device, it is easy to gather different cell density colonies in different sizes of micro-chambers using one homogeneous cell solution. As a demonstration, we show that the cell number of self-patterning MCF-7 colony is in proportion to the size of liquid-absorbing cavity in the device, from single cell to tens of cells. This device can easily be used to compare the cancer cells’ proliferation in different micro-environments, such as the same number of cells in micro-cavities with different sizes, or different numbers of cells in micro-cavities with the same size, or with different FBS concentrations. Our studies imply a plausible positive correlation between the local concentration of autocrine factors and tumor cell proliferation, which is also quantitative analyzed by a simple model.
Similar content being viewed by others
References
J.W. Allen, S.N. Bhatia, Formation of steady-state oxygen gradients in vitro: application to liver zonation. Biotechnol. Bioeng. 82, 253–262 (2003)
A.J. Almarza, K. A. Athanasiou, Effects of initial cell seeding density for the tissue engineering of the temporomandibular joint disc. Ann. Biomed. Eng. 33, 943–950 (2005)
J. El-ali, P.K. Sorger, K.F. Jensen, Cells on chips. Nature 442, 403–411 (2006)
K. Gupta, D.H. Kim, D. Ellison, C. Smith, A. Kundu, J. Tuan, K.Y. Suh, A. Levchenko, Lab-on-a-chip devices as an emerging platform for stem cell biology. Lab. Chip 10, 2019–2031 (2010)
P. Hamerlik, J.D. Lathia, R. Rasmussen, Q. Wu, J. Bartkova, M. Lee, P. Moudry, J. Bartek Jr., W. Fischer, J. Lukas, J.N. Rich, J. Bartek, Autocrine VEGF – VEGFR2 – Neuropilin-1 signaling promotes glioma stem-like cell viability and tumor growth. J. Exp. Med. 209, 507–520 (2012)
K. Herholz, U. Pietrzyk, J. Voges, R. Schröder, M. Halber, H. Treuer, V. Sturm, W.D. Heiss, Correlation of glucose consumption and tumor cell density in astrocytomas. J. Neurosurg. 79, 853–858 (1993)
R.W. Holly, Control of growth of mammalian cells in cell culture. Nature 258, 487–490 (1975)
T.H. Hsu, J.L. Xiao, Y.W. Tsao, Y.L. Kao, S.H. Huang, W.Y. Liao, C.H. Lee, Analysis of the paracrine loop between cancer cells and fibroblasts using a microfluidic chip. Lab. Chip 11, 1808–1814 (2011)
T.H. Hsu, Y.L. Kao, W.L. Lin, J.L. Xiao, P.L. Kuo, C.W. Wu, W.Y. Liao, C.H. Lee, The migration speed of cancer cells influenced by macrophages and myofibroblasts co-cultured in a microfluidic chip. Integr. Biol. 4, 177–182 (2012)
P.J. Hung, P.J. Lee, P. Sabounchi, R. Lin, L.P. Lee, Continuous perfusion microfluidic cell culture array for high-throughput cell-based assays. Biotechnol. Bioeng. 89, 1–8 (2004)
K. Kim, D. Dean, A.G. Mikos, J.P. Fisher, Effect of initial cell seeding density on early osteogenic signal expression of rat bone marrow stromal cells cultured on cross-linked poly(propylene fumarate) disks. Biomacromolecules 10, 1810–1817 (2009)
S.D. Kim, H.J. Kim, N.L. Jeon, Biological applications of microfluidic gradient devices. Integr. Biol. 2, 584–603 (2010)
C. Luo, X. Zhu, T. Yu, X. Luo, A fast cell loading and high-throughput microfluidic system for long-term cell culture in zero-flow environments. Biotechnol. Bioeng. 101, 190–195 (2008)
A. Maria, F. Macian, Autophagy, nutrition and immunology. Mol. Aspects Med. 33, 2–13 (2012)
S.M. Ong, C. Zhang, Y.C. Toh, S. Hyun, H. Loong, C. Tan, D. Noort, S. Park, H. Yu, A gel-free 3D microfluidic cell culture system. Biomaterials 29, 3237–3244 (2008)
A. Pluen, Y. Boucher, S. Ramanujan, T.D. Mckee, T. Gohongi, E. Tomaso, E.B. Brown, Y. Izumi, R.B. Campbell, D.A. Berk, R.K. Jain, Role of tumor – host interactions in interstitial diffusion of macromolecules: cranial vs. Subcutaneous tumors. PNAS 98, 4628–4633 (2001)
W. Saadi, S.J. Wang, F. Lin, N.L. Jeon, A parallel-gradient microfluidic chamber for quantitative analysis. Biomed. Microdev. 8, 109–118 (2006)
G.W. Si, W. Yang, S.Y. Bi, C.X. Luo, Q. Ouyang, A parallel diffusion-based microfluidic device for bacterial chemotaxis analysis. Lab. Chip 12, 1389–1394 (2012)
M.B. Sporn, G.J. Todaro, Autocrine secretion and malignant transformation of cells. N. Engl. J. Med. 303, 878–880 (1980)
P. Vaupel, F. Kallinowski, P. Okunieff, Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res. 49, 6449–6465 (1989)
G. Vunjak-novakovic, D.T. Scadden, Perspective biomimetic platforms for human stem cell research. Stem Cell 8, 252–261 (2011)
L. Wang, X.F. Ni, C.X. Luo, Z.L. Zhang, D.W. Pang, Y. Chen, Self-loading and cell culture in one layer microfluidic devices. Biomed. Microdev. 11, 679–684 (2009a)
L. Wang, I. Tran, K. Seshareddy, M.L. Weiss, M.S. Detamore, A comparison of human bone marrow–derived mesenchymal stem cells and human umbilical cord–derived mesenchymal stromal cells for cartilage tissue engineering. Tissue Eng. Part A 15, 2259–2266 (2009b)
E.W.K. Young, D.J. Beebe, Fundamentals of microfluidic cell culture in controlled microenvironments. Chem. Soc. Rev. 39, 1036–1048 (2010)
H. Yu, I. Meyvantsson, A. Shkel, D.J. Beebe, Diffusion dependent cell behavior in microenvironments. Lab. Chip 5, 1089–1095 (2005)
A. Zetterberg, G. Auer, Proliferative activity and cytochemical properties of nuclear chromatin related to local cell density of epithelial cells. Exp. Cell Res. 62, 262–270 (1970)
K. Zhang, P. Wong, L. Zhang, B. Jacobs, E.C. Borden, J.C. Aster, B. Bedogni, A Notch1–neuregulin1 autocrine signaling loop contributes to melanoma growth. Oncogene 31, 4609–4618 (2012)
H. Zhou, M.D. Weir, H.H.K. Xu, Effect of cell seeding density on proliferation and osteodifferentiation of umbilical cord stem cells on calcium phosphate cement-fiber scaffold. Tissue Eng. 17, 2603–2613 (2011)
Acknowledgments
We would like to thank X.J Kang for helpful discussions. This work is partially supported by the NSF of China (10721403, 11074009, 10721463, 11174012), the MOST of China (2009CB918500).
Author information
Authors and Affiliations
Corresponding authors
Electronic supplementary material
Below is the link to the electronic supplementary material.
ESM 1
(DOC 118 kb)
Rights and permissions
About this article
Cite this article
Yang, W., Li, Z., Zhang, W. et al. A novel density control device for the study of cancer cell autocrine effect. Biomed Microdevices 15, 683–689 (2013). https://doi.org/10.1007/s10544-013-9783-7
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10544-013-9783-7